SIDE EFFECTS OF PTU AND MMI IN THE TREATMENT OF HYPERTHYROIDISM: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Objective: The present study aimed to investigate the adverse effects of the anti-thyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Method: Qualitative analysis was performed for studies identified in literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control studies, randomized controlled trials, and retrospective cohort studies. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Results: Odds of liver function injury was higher in the PTU group than in the MMI/CMZ group (odds ratio [OR] 2.40; 95% Confidence Interval [CI] 1.16 to 4.96; P=0.02).Odds of elevated transaminase was much higher in the PTU group than in the MMI/CMZ group (OR 3.96; 95%CI 2.49 to 6.28; P<0.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash and urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy was higher in the MMI/CMZ group than in the PTU group (OR 1.29; 95%CI 1.09 to 1.53; P=0.003). Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy.